US20070087035A1 - Nutritional composition for wound healing - Google Patents
Nutritional composition for wound healing Download PDFInfo
- Publication number
- US20070087035A1 US20070087035A1 US10/596,159 US59615904A US2007087035A1 US 20070087035 A1 US20070087035 A1 US 20070087035A1 US 59615904 A US59615904 A US 59615904A US 2007087035 A1 US2007087035 A1 US 2007087035A1
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- US
- United States
- Prior art keywords
- composition
- total calories
- arginine
- proline
- source
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 230000029663 wound healing Effects 0.000 title claims abstract description 21
- 235000016709 nutrition Nutrition 0.000 title claims abstract description 19
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
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- A—HUMAN NECESSITIES
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A61P3/02—Nutrients, e.g. vitamins, minerals
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- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- This invention relates to a nutritional composition for promoting wound healing, particularly the healing of chronic wounds such as pressure ulcers (decubitus).
- the first phase is inflammation in which the clot forms and stops the bleeding from blood vessels followed by extravasation of mononuclear blood cells which clean the wound and remove debris.
- the next phase is the granulation phase in which fibroblasts proliferate and accumulate in the wound and produce collagen to assist in wound closure. This phase is characterised by high metabolic activity.
- epithelial cells begin to cover the wound.
- Delayed or impaired wound healing is a problem for health care professionals and patients as it results in increased treatment times and stays in healthcare facilities and distress to patients.
- the process of wound healing can be interrupted in any of the phases described above as a result of factors such as infection or malnutrition.
- the pressure ulcers which frequently afflict elderly and bed-ridden patients are a particular concern and these categories of patients are often found to be suffering from malnutrition. Indeed, all patients with acute or chronic wounds exhibit increased nutritional requirements, displaying a need for increased nutrients and energy as compared with individuals not challenged by such metabolic stresses. If these patients are malnourished before suffering wounds, the wounds may simply fail to heal.
- arginine is also a precursor for the formation of nitric oxide which acts as a vasodilator and enhances growth hormone secretion. It is not desirable for critically ill individuals to be exposed to high amounts of nitric oxide and yet this will inevitably happen if such individuals receive nutritional supplements containing high levels of arginine—see, for example L. Cynober, Curr Opin Clin Nutr Metab Care. 6:189-93 2003. Moreover, it is quite likely that a high proportion of elderly, bedridden or critically ill patients at risk of developing pressure sores will also suffer from conditions for which high levels of nitric oxide are contra-indicated (J. Takala et al., N Engl J Med 341:785-792 1999).
- the present invention provides a nutritional composition for promoting wound healing comprising a protein source, a lipid source and a carbohydrate source wherein no more than 1.8% of the total calories of the composition derive from arginine and wherein the protein source includes proline in an amount of at least 3% of the total calories of the composition.
- the present invention provides a method of providing nutritional support to a patient with an acute or chronic wound comprising the step of administering a therapeutically effective amount of a nutritional composition comprising a protein source, a lipid source and a carbohydrate source wherein no more than 1.8% of the total calories of the composition derive from arginine and wherein the protein source includes proline in an amount of at least 3% of the total calories of the composition.
- the present invention provides the use of a protein source, a lipid source and a carbohydrate source for the manufacture of a therapeutic formulation for promoting wound healing wherein no more than 1.8% of the total calories of the formulation derive from arginine and wherein the protein source includes proline in an amount of at least 3% of the total calories of the formulation.
- the present inventor believes that from a therapeutic/nutritional approach, attempts to modulate this phase carry high risks and that the granulation phase offers better potential for nutritional intervention.
- this phase new connective tissue is synthesised and more than 80% of this tissue is composed of collagen.
- Collagen is rich in the amino acids proline (about 22%) and glycine (about 33%) and the presence of these amino acids is rate limiting for collagen formation, that is to say, collagen cannot be efficiently formed if they are not available in sufficient quantity.
- the normal diet contains only about 3% in total of these amino acids and it will be appreciated that individuals who have suffered wounds may ingest even less of them, particularly as proline is not generally regarded as an essential dietary amino acid.
- composition of the present invention is therefore supplemented with proline in a quantity sufficient to facilitate collagen synthesis. It is particularly suitable for the amelioration of pressure ulcers but may also be used in the management of acute wounds including before and after surgery.
- composition of the present invention does not need to be supplemented with arginine—of course some arginine is likely to be present as part of the protein source. However, it is widely believed that arginine also has a role in the inflammatory phase of wound healing and, for this reason, the composition of the present invention is preferably supplemented with small amounts of arginine subject always to the requirement that arginine must account for no more than 1.8% of the total calories of the composition.
- composition of the present invention contains sources of protein, lipids and carbohydrate and may be administered orally or enterally.
- the composition preferably provides about 1.25 kcal/ml.
- Protein is essential to healing as tissue damage results in a catabolic response that includes a requirement for a larger proportion of total calories as protein than is required by the general population.
- enteral fortification employing large quantities of protein can accelerate the synthesis of visceral proteins and so the protein source of the present invention preferably constitutes at least 25% of the total energy content of the composition, more preferably at least 28%.
- protein sources may be used including intact protein sources such as casein or whey as well as hydrolysed proteins, free amino acids and even mixtures of intact and hydrolysed proteins and/or free amino acids, in each case supplemented with free proline and, optionally, free arginine.
- the protein source of the present invention is selected to yield the highest amount of proline in the proteins so as to minimise the amount that needs to be added as the free amino acid.
- proline constitutes at least 3.5% of the calories of the composition of the present invention. At this level of contribution to total calories, the composition will need to be supplemented by about 3.0% (by weight of the protein source) proline.
- the total calories/gram of nitrogen of the composition of the invention is preferably about 160:1.
- the total non-protein calories/gram of nitrogen is preferably about 110:1.
- the composition of the present invention also includes a lipid source.
- Lipids or fats are the primary source of stored energy in the body and energy from fat metabolism is used in all normal cell functions. As far as wound healing is concerned, fat metabolism results in the formation of prostaglandins and other regulators of the inflammatory process.
- the lipid source used in the present invention preferably constitutes about 20% of the total energy content of the composition. Of this 20%, preferably about 8% is constituted by mono- and di-glycerides of fatty acids.
- the ratio of n ⁇ 6 to n ⁇ 3 fatty acids is preferably between 4:1 and 10:1, more preferably about 7:1.
- the composition of the present invention also includes a carbohydrate source.
- Glucose is the primary fuel for cellular metabolism of many tissues including leucocytes, macrophages and fibroblasts all of which are involved in the wound healing process. Glucose is needed to meet the specific metabolic demands of wound healing.
- the carbohydrate source used in the present invention preferably constitutes about 50% of the total energy content of the composition. Suitable sources of carbohydrate are maltodextrin and sucrose. Preferably, the carbohydrate source is substantially free of lactose.
- Vitamins, minerals and trace elements are also important in the wound healing process.
- the composition of the present invention at least complies with the compositional criteria set out in Directive 1999/21/EC on Dietary Foods for Special Medical Purposes as regards these micronutrients.
- certain micronutrients are particularly important for wound healing and therefore the composition of the present invention preferably contains more than the recommended minimum levels of vitamins C and E, manganese, zinc and selenium.
- EXAMPLE 1 Caloric density 1.25 g/ml Protein 30% of kcal of which (by weight):- sodium caseinate 50% milk protein 45% concentrate free L-proline 3% free L-arginine 2% total L-proline 12.4% of protein source total L-arginine 5.0% of protein source Caloric contribution 3.7% of total proline Caloric contribution 1.5% of total arginine Lipids 20% of kcal of which rapeseed oil 35% corn oil 34% soya oil 20% mono and 8% di-glycerides of fatty acids milk fat 3% n-6:n-3 7.2:1 Carbohydrate 50% of kcal of which corn syrup 52% sucrose 43% starch 3% lactose 2% Vitamin C 125 mg/100 ml Vitamin E 7.5 mg ⁇ -tocopherol equivalents/100 ml Manganese 1.9 mg/100 ml Zinc 3.7 mg/100 ml Selen
- compositions will also contain other micronutrients of the type conventionally found in enteral compositions in accordance with EC Directive 1999/21/EC as well as flavourings such as coffee or vanilla, emulsifiers, thickeners and stabilizers of the type conventionally found in enteral compositions.
- the nutritional composition may be produced by conventional methods.
- the protein source and the lipid source are dissolved in water, preferably water which has been subjected to reverse osmosis, to form a liquid mixture.
- Emulsifiers may be dissolved in the lipid source prior to blending if desired.
- a food grade emulsifier from a vegetable source is used.
- the temperature of the water is conveniently about 50° C. to about 80° C. to aid dispersal of the ingredients.
- Commercially available liquefiers may be used to form the liquid mixture.
- pH of the liquid mixture is adjusted to about 6.3 to 7 with food grade hydroxides.
- the carbohydrate source is added together with other easily dissolvable ingredients including, for example, vitamins, minerals, flavourings and colorants.
- the liquid mixture may then be thermally treated to reduce bacterial loads (pasteurized). This may be carried out by steam injection or by heat exchanger; for example a plate heat exchanger.
- an ultra heat treatment is preferably conducted after pre-heating to 50-85° C.
- UHT ultra heat treatment
- an indirect UHT treatment may be conducted at 140-155° C. for 5-8 s, in a tube heat exchanger.
- the liquid mixture may then be cooled to about 60° C. to about 85° C.; for example by flash cooling.
- the liquid mixture is then homogenized and the resulting homogenised milky liquid may be aseptically filled into suitable containers such as 200 ml cups for oral feeding. Aseptic filling of the containers may be carried out by cooling the liquid mixture.
- the homogenised mixture can be evaporated and dried to powder; for example by spray drying. Conventional procedures may be used.
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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EP03029505.9 | 2003-12-20 | ||
EP03029505.9A EP1543735B1 (de) | 2003-12-20 | 2003-12-20 | Lebensmittelzusammensetzung für die wundheilung |
PCT/EP2004/013787 WO2005060768A1 (en) | 2003-12-20 | 2004-12-03 | Nutritional composition for wound healing |
Related Parent Applications (1)
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PCT/EP2004/013787 A-371-Of-International WO2005060768A1 (en) | 2003-12-20 | 2004-12-03 | Nutritional composition for wound healing |
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US13/116,827 Continuation US20110230400A1 (en) | 2003-12-20 | 2011-05-26 | Nutritional composition for wound healing |
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US20070087035A1 true US20070087035A1 (en) | 2007-04-19 |
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US13/116,827 Abandoned US20110230400A1 (en) | 2003-12-20 | 2011-05-26 | Nutritional composition for wound healing |
US14/464,257 Abandoned US20140357553A1 (en) | 2003-12-20 | 2014-08-20 | Nutritional composition for wound healing |
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US13/116,827 Abandoned US20110230400A1 (en) | 2003-12-20 | 2011-05-26 | Nutritional composition for wound healing |
US14/464,257 Abandoned US20140357553A1 (en) | 2003-12-20 | 2014-08-20 | Nutritional composition for wound healing |
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US (3) | US20070087035A1 (de) |
EP (1) | EP1543735B1 (de) |
JP (1) | JP2007515417A (de) |
CN (1) | CN1893839B (de) |
AR (1) | AR046969A1 (de) |
BR (1) | BRPI0417875A (de) |
CA (1) | CA2546472A1 (de) |
DK (1) | DK1543735T3 (de) |
ES (1) | ES2550608T3 (de) |
IL (1) | IL175478A0 (de) |
TW (1) | TWI403276B (de) |
WO (1) | WO2005060768A1 (de) |
ZA (1) | ZA200605983B (de) |
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JP5577098B2 (ja) * | 2006-12-21 | 2014-08-20 | アムジエン・インコーポレーテツド | ポリペプチドを含有する安定な緩衝化された製剤 |
JP5118915B2 (ja) * | 2007-07-31 | 2013-01-16 | 森永乳業株式会社 | 褥瘡改善剤 |
TWI561175B (en) * | 2011-03-31 | 2016-12-11 | Meiji Co Ltd | Flowable nutrition composition containing l-arginine and method for producing the same |
JOP20190146A1 (ar) | 2016-12-19 | 2019-06-18 | Axcella Health Inc | تركيبات حمض أميني وطرق لمعالجة أمراض الكبد |
CN107319574A (zh) * | 2017-08-03 | 2017-11-07 | 江西美庐乳业集团有限公司 | 一种有益于烧伤创伤人群康复的蛋白组件食品 |
EP3668499A1 (de) | 2017-08-14 | 2020-06-24 | Axcella Health Inc. | Aminosäurezusammensetzungen zur behandlung von lebererkrankungen |
CN112839643A (zh) | 2018-06-20 | 2021-05-25 | 胺细拉健康公司 | 用于治疗肌肉中脂肪浸润的组合物及方法 |
DE102018124227A1 (de) | 2018-10-01 | 2020-04-02 | sanaFactur GmbH | Zubereitung zur Verbesserung körpereigener Wundheilung |
CN116687003A (zh) * | 2022-02-24 | 2023-09-05 | 亚宝药业集团股份有限公司 | 一种用于老年消化道肿瘤切除术后患者的营养组合物 |
CN115918914A (zh) * | 2022-12-01 | 2023-04-07 | 宝健(北京)生物技术有限公司 | 一种含复合蛋白的口服营养补充剂,制备及应用 |
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US5053387A (en) * | 1987-02-20 | 1991-10-01 | Shriners Hospitals For Crippled Children | Omega-3 fatty acids in traumatic injury treatment |
US5384306A (en) * | 1992-05-04 | 1995-01-24 | H. C. Starck Gmbh And Co. | Fine-particle oxide ceramic powders |
US5714472A (en) * | 1993-12-23 | 1998-02-03 | Nestec Ltd. | Enternal formulation designed for optimized nutrient absorption and wound healing |
US5733884A (en) * | 1995-11-07 | 1998-03-31 | Nestec Ltd. | Enteral formulation designed for optimized wound healing |
US6194379B1 (en) * | 1998-05-01 | 2001-02-27 | Abbott Laboratories | Elemental enteral formula |
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US5198465A (en) * | 1991-06-19 | 1993-03-30 | Dioguardi Francesco S | Compositions based on amino acids for preventing and treating precursor deficiencies in the synthesis of collagen |
US5384308A (en) * | 1993-06-14 | 1995-01-24 | Henkin; R. I. | Composition and method for enhancing wound healing |
US5827874A (en) * | 1995-05-05 | 1998-10-27 | Meyer; Hans | Methods of treating pain and inflammation with proline |
GB0009056D0 (en) * | 2000-04-12 | 2000-05-31 | Nestle Sa | Composition comprising free amino acids |
IT1318556B1 (it) * | 2000-06-07 | 2003-08-27 | Solartium Establishment | Composizione farmaceutica a base di prolina, glicina e lisina utilenella terapia per la cicatrizzazione delle ferite e delle lesioni |
GB0016045D0 (en) * | 2000-06-29 | 2000-08-23 | Laxdale Limited | Therapeutic combinations of fatty acids |
ITTO20010804A1 (it) * | 2001-08-08 | 2003-02-08 | Professional Dietetics Srl | Composizioni a base di aminoacidi, idonee alla terapia per la cicatrizzazione e/o riparazione di ferite e lesioni, in particolare per l'appl |
AU2003214719A1 (en) * | 2002-03-08 | 2003-09-22 | Universiteit Leiden | Use proline and its functional equivalentsfor quenching ros and/ or radicals |
DE10221403A1 (de) * | 2002-05-14 | 2003-12-04 | Kyberg Pharma Vertriebs Gmbh & | Diätetische und pharmazeutische Zusammensetzungen, ihre Herstellung und ihre Verwendung |
US20040087490A1 (en) * | 2002-09-20 | 2004-05-06 | Troup John P. | Nutritional compositions |
-
2003
- 2003-12-20 ES ES03029505.9T patent/ES2550608T3/es not_active Expired - Lifetime
- 2003-12-20 EP EP03029505.9A patent/EP1543735B1/de not_active Expired - Lifetime
- 2003-12-20 DK DK03029505.9T patent/DK1543735T3/en active
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2004
- 2004-12-03 CN CN2004800371701A patent/CN1893839B/zh not_active Expired - Fee Related
- 2004-12-03 WO PCT/EP2004/013787 patent/WO2005060768A1/en active Application Filing
- 2004-12-03 BR BRPI0417875-0A patent/BRPI0417875A/pt active Search and Examination
- 2004-12-03 CA CA002546472A patent/CA2546472A1/en not_active Abandoned
- 2004-12-03 JP JP2006544267A patent/JP2007515417A/ja active Pending
- 2004-12-03 US US10/596,159 patent/US20070087035A1/en not_active Abandoned
- 2004-12-17 TW TW093139499A patent/TWI403276B/zh not_active IP Right Cessation
- 2004-12-20 AR ARP040104799A patent/AR046969A1/es unknown
-
2006
- 2006-05-08 IL IL175478A patent/IL175478A0/en unknown
- 2006-07-19 ZA ZA200605983A patent/ZA200605983B/xx unknown
-
2011
- 2011-05-26 US US13/116,827 patent/US20110230400A1/en not_active Abandoned
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2014
- 2014-08-20 US US14/464,257 patent/US20140357553A1/en not_active Abandoned
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US5053387A (en) * | 1987-02-20 | 1991-10-01 | Shriners Hospitals For Crippled Children | Omega-3 fatty acids in traumatic injury treatment |
US5384306A (en) * | 1992-05-04 | 1995-01-24 | H. C. Starck Gmbh And Co. | Fine-particle oxide ceramic powders |
US5714472A (en) * | 1993-12-23 | 1998-02-03 | Nestec Ltd. | Enternal formulation designed for optimized nutrient absorption and wound healing |
US5733884A (en) * | 1995-11-07 | 1998-03-31 | Nestec Ltd. | Enteral formulation designed for optimized wound healing |
US6194379B1 (en) * | 1998-05-01 | 2001-02-27 | Abbott Laboratories | Elemental enteral formula |
Also Published As
Publication number | Publication date |
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DK1543735T3 (en) | 2015-11-02 |
CN1893839A (zh) | 2007-01-10 |
ES2550608T3 (es) | 2015-11-11 |
EP1543735A1 (de) | 2005-06-22 |
ZA200605983B (en) | 2007-12-27 |
TW200528035A (en) | 2005-09-01 |
WO2005060768A1 (en) | 2005-07-07 |
IL175478A0 (en) | 2006-09-05 |
CN1893839B (zh) | 2010-06-09 |
JP2007515417A (ja) | 2007-06-14 |
BRPI0417875A (pt) | 2007-04-27 |
AR046969A1 (es) | 2006-01-04 |
US20110230400A1 (en) | 2011-09-22 |
US20140357553A1 (en) | 2014-12-04 |
CA2546472A1 (en) | 2005-07-07 |
EP1543735B1 (de) | 2015-10-07 |
TWI403276B (zh) | 2013-08-01 |
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